Clinical Scenario 2: Metastatic CSCC with Significant Comorbidities

Dr. Hamid presents an 86-year-old retired construction worker with diabetes, hypertension, and prior basal cell carcinoma, now with a 2.8 cm facial CSCC lesion and imaging-confirmed pulmonary metastases. He has received maximum prior radiation dose. Performance status is ECOG 1; laboratory values include HbA1c 8.2%, creatinine 1.8 mg/dL, ejection fraction 45%, and mildly restricted pulmonary function.

Dr. Zeitouni notes the complexity of this case: metastatic disease, advanced age, multiple significant comorbidities including cardiomyopathy and baseline renal impairment, and prior radiation. Following tumor board discussion and multidisciplinary input, systemic immunotherapy is the appropriate direction. Given the extensive comorbidities and safety considerations, cosibelimab is again favored for its more favorable immune-mediated adverse event profile. She raises the possibility of extended dosing intervals (such as every 6 weeks rather than every 2-3 weeks) as a potential schedule modification to discuss with medical oncology colleagues for this patient.

NP Schollenberger frames the goals-of-care conversation around the patient's perspective: the facial mass will become increasingly symptomatic if untreated, leading to painful, draining, and locally destructive effects. Although response rates in the metastatic setting are slightly lower than in locally advanced disease, approximately 50% of patients still achieve meaningful responses. Practical management principles include a low threshold to hold therapy for emerging toxicities, prompt imaging for any respiratory symptoms given his restricted pulmonary function and reduced ejection fraction, and careful cardiovascular monitoring. Early toxicity intervention before grade escalation is particularly critical in this population.

When patients require treatment interruption or discontinuation, Dr. Zeitouni notes that discontinuation rates with cosibelimab are approximately 8%, meaning that most patients are able to remain on therapy long enough to derive clinical benefit. For patients who progress on or are intolerant of checkpoint inhibitor therapy, emerging investigational approaches include combining immune checkpoint inhibitors with targeted therapies, oncolytic viruses, and EGFR inhibitors, alongside continued clinical trial enrollment as the preferred strategy.